Neurodegenerative diseases such as Alzheimer's disease are believed to involve changes in the brain that begin before the onset of symptoms, but the mechanisms remain unclear. This research aims to establish a large-scale cellomics platform to capture these ultra-early changes. To identify minute lesions often missed in conventional 2D tissue sections, we will develop an advanced tissue clearing technology and a large-scale light-sheet microscopy designed for large specimens, including human autopsy brains. This will enable high-speed screening of all cells within a specimen to identify subtle pathological changes that occur before neuronal loss. By integrating the information on these early lesions with molecular data, we aim to elucidate the pathology of early neurodegeneration.